Oseltamivir Phosphate, widely known under the trade designation TAMIFLU, is targeted for use as an antiviral compound to prevent and/or treat influenza infections. Oseltamivir Phosphate has been described in C. U. Kim et al., J. Med. Chem. 1998, 41, 2451; C. U. Kim et al., J. Am. Chem. Soc. 1997, 119,681; and M. Federspiel et al., Organic Process Research & Development 1999, 3, 266-274, the entireties of which are incorporated herein by reference in their respective entireties for all purposes.
Oseltamivir Phosphate has the formula
and is the prodrug of the potent neuraminidase inhibitor having the formula:

The literature describes preparing Oseltamivir Phosphate in multistep syntheses starting from either quinic acid:
or shikimic acid:
See M. Federspiel et al., Organic Process Research & Development 1999, 3, 266-274.
Synthesis from quinic acid generally was proposed first. The synthesis via quinic acid was satisfactory for the production of kilogram quantities of Oseltamivir Phosphate, but as the demand for Oseltamivir Phosphate increased and continues to increase, better synthesis techniques more suitable for larger scale production are desired. Syntheses of Oseltamivir Phosphate starting from shikimic acid were developed as a result of this desire. Shikimic acid-based syntheses offer great potential due to the fact that the desired carbon-carbon double bond is already present, whereas the double bond has to be created when starting from quinic acid. Having a starting material that already incorporates the desired double bond bypasses the regioselective dehydration associated with developing this functionality in the quinic acid routes.
The article by M. Federspiel cited herein describes two potential synthesis routes of Oseltamivir Phosphate starting from shikimic acid. One synthesis involves the direct ketalization of a shikimic acid ester. The other proceeds via an acetonide intermediate. Even though the acetonide route involves more steps and more isolations, the authors strongly prefer the acetonide route over the direct ketalization route. The authors discarded the direct ketalization route as impractical because the intermediates (the ketalized shikimic acid ester and the mesylated, ketalized shikimic acid ester) are oils and had to be carried through in crude form until the step in which the crystalline epoxide could be purified efficiently.
In the meantime, the demand for Oseltamivir Phosphate continues to be very strong. There remains a strong need, consequently, to develop improved synthesis routes of Oseltamivir Phosphate.